Pancreatic cancer mortality trends in the United States: how much have we moved the needle?

Background: Despite advances made in pancreatic cancer treatment, the extent of progress made in pancreatic cancer mortality at the population level remains unclear. Our cross-sectional study sought to measure trends in pancreatic cancer mortality in the United States in the last 2 decades. Methods: Patients with pancreatic cancer mortality from 1999 to 2020 were analyzed from the Centers for Disease Control and Prevention's Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER). Age-adjusted mortality rates (AAMRs) per 100,000 individuals were measured. We used joinpoint trend analysis to determine average annual percent change (AAPC) in AAMR trends. Results: From 1999 to 2020, pancreatic cancer accounted for 809,197 deaths. Overall, the AAMRs of pancreatic cancer increased from 20.74 per 100,000 individuals in 1999 to 21.60 per 100,000 individuals in 2020. The highest AAMR was recorded in non-Hispanic Black males (30.11 per 100,000 individuals), and the lowest, in non-Hispanic White females (18.51 per 100,000 individuals). Patients aged 75-84 years had the highest AAMR (6.87 per 100,000 individuals) compared to the younger patients. The highest AAMR was observed in the Northeast region (22.07 per 100,000 individuals) and rural regions (21.29 per 100,000 individuals). Conclusions: There was no improvement in pancreatic cancer mortality in the last two decades. These findings emphasize the importance of efforts to increase access to multidisciplinary cancer care with the realization that without it, improvements in treatment standards will not translate to lower cancer mortality at the population level.

Dendritic cell vaccine for glioblastoma: an updated meta-analysis and trial sequential analysis.

BACKGROUND: Dendritic cell (DC) vaccine is an emerging immunotherapy that could potentially improve glioblastoma survival. The first phase III clinical trial of DC vaccine was recently published. This meta-analysis aims to update and reappraise existing evidence on the efficacy of DC vaccine in patients with glioblastoma. METHODS: We searched PubMed, Embase, and Cochrane Library for clinical trials of DC vaccine for glioblastoma. The quality of the studies was assessed using the RoB 2.0 and ROBINS-I tools. The results of overall survival (OS) and progression-free survival (PFS) were pooled using hazard ratios (HRs) with corresponding 95% confidence intervals (CI). Summary effects were evaluated using random effects models. Trial sequential analysis (TSA) was performed. RESULTS: Seven clinical trials involving 3,619 patients were included. DC vaccine plus standard care was associated with significantly improved OS (HR = 0.71; 95% CI, 0.57 - 0.88) and PFS (HR = 0.65; 95% CI, 0.43 - 0.98). In the subgroup of newly diagnosed glioblastoma, DC vaccine was associated with improved PFS (HR = 0.59; 95% CI, 0.39 - 0.90). TSA of OS showed that the cumulative z-score line for the DC vaccine crossed the benefit boundary and reached the required sample size. TSA of PFS and subgroup analysis of newly diagnosed glioblastoma showed that the required sample size was not reached. CONCLUSIONS: This updated meta-analysis, which included the first phase III trial of a DC vaccine for glioblastoma, demonstrated that the DC vaccine was associated with improved OS. Moreover, TSA showed that the required sample size was reached, indicating a true-positive result. Future studies are required for patient subgroups with newly diagnosed and recurrent glioblastoma.

Clinical performance of Bladder EpiCheck™ versus voided urine cytology for detecting recurrence of nonmuscle invasive bladder cancer: Systematic review and meta-analysis.

BACKGROUND: Nonmuscle invasive bladder cancer (NMIBC) has a favorable prognosis but has high propensity for recurrence. Recent development in one of the urinary biomarker tests, Bladder EpiCheck™, offers a noninvasive and accurate method to detect NMIBC recurrence. In this study, we aimed to compare the diagnostic performance of Bladder EpiCheck™ with urine cytology to detect NMIBC recurrence. METHODS: We performed a systematic review search through PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus from inception to July 2023. Diagnostic accuracy was defined by sensitivity, negative predictive value (NPV), specificity, and positive predictive value (PPV). RESULTS: A total of 6 studies involving 1588 patients were included. Bladder EpiCheck™ has a sensitivity and specificity of 0.81 (95% CI: 0.63-0.91; I2: 43%) and 0.87 (95% CI: 0.83-0.91; I2: 20%), respectively. On the other hand, urine cytology has a sensitivity and specificity of 0.63 (95% CI: 0.29-0.87; I2: 61%) and 0.97 (95% CI: 0.78-1.00; I2: 79%), respectively. EpiCheck™ has a higher NPV (0.94 (95% CI: 0.87-0.97) vs. 0.84 (95% CI: 0.80-0.87) though a lower PPV (0.62 (95% CI: 0.45-0.76) vs. 0.87 (95% CI: 0.56-0.97) than urine cytology. In our subgroup analysis, the sensitivity of Bladder EpiCheck™ for detecting high-grade tumors improved to 0.90 (95% CI: 0.83-0.94) while that for urine cytology improved to 0.72 (95% CI: 0.50-0.87). CONCLUSION: Bladder EpiCheck™ has a high sensitivity and NPV for detecting recurrence among patients with NMIBC.

Rate of Sodium Correction and Osmotic Demyelination Syndrome in Severe Hyponatremia: A Meta-Analysis.

Introduction: Current guidelines recommend limiting the rate of correction in patients with severe hyponatremia to avoid severe neurologic complications such as osmotic demyelination syndrome (ODS). However, published data have been conflicting. We aimed to evaluate the association between rapid sodium correction and ODS in patients with severe hyponatremia. Materials and methods: We searched PubMed, Embase, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials from inception to November 2023. The primary outcome was ODS and the secondary outcomes were in-hospital mortality and length of hospital stay. Results: We identified 7 cohort studies involving 6,032 adult patients with severe hyponatremia. Twenty-nine patients developed ODS, resulting in an incidence rate of 0.48%. Seventeen patients (61%) had a rapid correction of serum sodium in the first or any 24-hour period of admission. Compared with a limited rate of sodium correction, a rapid rate of sodium correction was associated with an increased risk of ODS (RR, 3.91 [95% CI, 1.17 to 13.04]; I2 = 44.47%; p = 0.03). However, a rapid rate of sodium correction reduced the risk of in-hospital mortality by approximately 50% (RR, 0.51 [95% CI, 0.39 to 0.66]; I2 = 0.11%; p < 0.001) and the length of stay by 1.3 days (Mean difference, -1.32 [95% CI, -2.54 to -0.10]; I2 = 71.47%; p = 0.03). Conclusions: Rapid correction of serum sodium may increase the risk of ODS among patients hospitalized with severe hyponatremia. However, ODS may occur in patients regardless of the rate of serum sodium correction.

The comparative efficacy and safety of factor Xa inhibitors and warfarin for primary thromboprophylaxis in multiple myeloma patients undergoing immunomodulatory therapy.

There are limited data on the optimal choice of anticoagulation in multiple myeloma (MM) patients receiving immunomodulatory drugs (IMiDs). We conducted a propensity score-matched cohort study using the TriNetX database to compare the efficacy and safety of factor Xa inhibitors and warfarin in this patient population. Compared to warfarin, factor Xa inhibitors had a similar risk of deep vein thrombosis (hazard ratio [HR]: 1.11 [95% CI: 0.50-2.46]) or pulmonary embolism (HR: 1.08 [95% CI: 0.59-2.00]). There were no differences in the risk of gastrointestinal or intracranial bleeding. Factor Xa inhibitor-treated patients had lower all-cause mortality (HR: 0.56 [95% CI: 0.36-0.86]) compared with warfarin. These data suggest that factor Xa inhibitors had similar safety and efficacy compared with warfarin for MM patients on IMiDs.

Periodontitis is an immune-related adverse event associated with immune checkpoint inhibitors: A multi-center cohort study.

Immune checkpoint inhibitors (ICIs) cause immune-related adverse events (irAEs) across various organ systems including oral health complications such as dry mouth and stomatitis. In this study, we aimed to determine the risk of periodontitis among patients on immune checkpoint inhibitors (ICIs) and to test the associations between ICI-associated periodontitis and other immune-related adverse events (irAEs). We performed a retrospective cohort study involving adult cancer patients between January 2010 and November 2021. Patients on an ICI were propensity score-matched to patients not on an ICI. The primary outcome was the occurrence of periodontitis. ICIs included programmed cell death 1 (PD-1) inhibitors programmed cell death ligand 1 (PD-L1) inhibitors, and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors. The risk of periodontitis following ICI use was derived through a Cox proportional hazard model and Kaplan-Meier survival analysis. Overall, 868 patients on an ICI were matched to patients not on an ICI. Among the ICI cohort, 41 (4.7 %) patients developed periodontitis. The incidence rate of periodontitis was significantly higher in patients on an ICI than in patients not on an ICI (55.3 vs 25.8 per 100 patient-years, incidence rate ratio = 2.14, 95 % CI = 1.38-3.33). Both the use of PD-L1 inhibitors (multivariate HR = 2.5, 95%CI = 1.3-4.7) and PD-1 inhibitors (multivariate HR = 2.0, 95%CI = 1.2-3.2) were associated with the risk of periodontitis. The presence of immune-related periodontitis was associated with better overall survival (not reached vs 17 months, log-rank p-value<0.001), progression-free survival (14.9 vs 5.6 months, log-rank p-value = 0.01), and other concomitant immune-related cutaneous adverse events. In conclusion, ICI was associated with an increased risk of periodontitis. Immune-related periodontitis as an irAE was associated with better cancer survival and concomitant cutaneous irAEs.

Thromboprophylaxis for outpatients with COVID-19: a Systematic Review and Meta-analysis.

Patients with COVID-19 develop an increased risk of thromboembolism. Thromboprophylaxis is recommended for hospitalized COVID-19 patients, but the role of thromboprophylaxis in outpatients with COVID-19 is less well defined. We conducted a systematic review and meta-analysis to evaluate the safety and efficacy of thromboprophylaxis among outpatients with COVID-19. We searched PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus from inception to August 2023. The outcomes of interest were venous thromboembolic events including deep venous thrombosis and pulmonary embolism, all-cause mortality, cardiovascular events, hospitalization, major bleeding events, and non-major bleeding events. We included 6 trials comprising 3352 patients. Patients who received thromboprophylaxis had an approximately 70% reduction in venous thromboembolism (RR, 0.28 [95% CI, 0.08 to 0.93]) compared to patients who did not receive thromboprophylaxis. The risk of mortality (RR, 0.79 [95% CI, 0.35 to 1.77]), cardiovascular events (RR, 0.91 [95% CI, 0.30 to 2.73]), and hospitalization (RR, 1.09 [95% CI, 0.81 to 1.47]) were similar between the two groups. Patients who received thromboprophylaxis had a higher risk of non-major bleeding (RR, 3.48 [95% CI, 1.72 to 7.05) compared to patients who did not receive thromboprophylaxis. Thromboprophylaxis reduced the risk of venous thromboembolism but not mortality, cardiovascular events, or hospitalization among outpatients with COVID-19.

The impact of sodium-glucose cotransporter-2 inhibitors on outcome of patients with diabetes mellitus and colorectal cancer.

BACKGROUND AND AIM: Patients with type 2 diabetes mellitus (T2DM) have a higher risk of colorectal cancer (CRC), and those with diagnosed CRC have a poorer prognosis compared with individuals with normal glucose levels. The inhibition of sodium-glucose cotransporter 2 (SGLT2) channels has been associated with a reduction in tumor proliferation in preclinical studies. We aimed to investigate the impact of sodium-glucose cotransporter 2 inhibitors (SGLT2i) on the outcome of T2DM patients with colorectal cancer. METHODS: We performed a retrospective cohort study comprising adult patients with T2DM and colorectal adenocarcinoma. SGLT2i recipients were matched to non-SGLT2i recipients in a 1:1 ratio based on age, sex, and cancer stage. The primary outcome was overall survival (OS) and progression-free survival (PFS), and the secondary outcomes were previously reported serious adverse events associated with SGLT2i. RESULTS: We identified 1347 patients with T2DM and colorectal adenocarcinoma, from which 92 patients in the SGLT2i cohort were matched to the non-SGLT2i cohort. Compared to non-SGLT2i recipients, SGLT2i recipients had a higher rate of 5-year OS (86.2% [95% CI: 72.0-93.5] vs 62.3% [95% CI: 50.9-71.8], P = 0.013) and 5-year PFS (76.6% [95% CI: 60.7-86.7] vs 57.0% [95% CI: 46.2-66.4], P = 0.021). In Cox proportional hazard analyses, SGLT2i were associated with a 50-70% reduction in all-cause mortality and disease progression. SGLT2i were not associated with an increased risk of serious adverse events. CONCLUSION: SGLT2i were associated with a higher rate of survival in T2DM patients with colorectal cancer.

Impact of different corticosteroids on severe community-acquired pneumonia: a systematic review and meta-analysis.

OBJECTIVES: Randomised controlled trials (RCTs) have demonstrated conflicting results regarding the effects of corticosteroids on the treatment of severe community-acquired pneumonia (CAP). We aimed to investigate the efficacy and safety of different corticosteroids on patients who were hospitalised for severe CAP. METHODS: We performed a systematic search through PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus from inception to May 2023. The primary outcome was all-cause mortality. Data analysis was performed using a random-effects model. RESULTS: A total of 10 RCTs comprising 1962 patients were included. Corticosteroids were associated with a lower rate of all-cause mortality (risk ratio (RR), 0.70 (95% CI 0.54 to 0.90); I2=0.00%). When stratified into different corticosteroid types, hydrocortisone was associated with an approximately 50% lower mortality risk (RR, 0.48 (95% CI 0.32 to 0.72); I2=0.00%). However, dexamethasone, methylprednisolone or prednisolone were not associated with an improvement in mortality. Furthermore, hydrocortisone was associated with a reduction in the rate of mechanical ventilation, acute respiratory distress syndrome, shock and duration of intensive care unit stay. These trends were not observed for dexamethasone, methylprednisolone or prednisolone. Corticosteroids were not associated with an increased risk of adverse events including gastrointestinal bleeding, secondary infection or hyperglycaemia. CONCLUSIONS: The use of hydrocortisone, but not other types of corticosteroids, was associated with a reduction in mortality and improvement in pneumonia outcomes among patients hospitalised with severe CAP.PROSPERO registration numberCRD42023431360.

The Effect of Exercise on Cardiotoxicity in Women with Breast Cancer Receiving Anthracycline-Based Chemotherapy: A Systematic Review and Meta-Analysis.

INTRODUCTION: Breast cancer is the most common cancer in women with a 5-year survival over 90%. However, anthracycline-based chemotherapy causes significant cardiotoxicity often requiring discontinuation of chemotherapeutic regimen among breast cancer survivors. We conducted a systematic review and meta-analysis to evaluate the efficacy of exercise training in mitigating anthracycline-related cardiotoxicity among women with breast cancer. METHODS: We searched PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus databases. The outcomes of interest were left ventricular ejection fraction (LVEF), global longitudinal strain (GLS), early to atrial filling velocity (E/A) ratio, maximal oxygen consumption (VO2 max), and cardiac output (CO). We used the Cochrane risk-of-bias tool for randomized trials (RoB 2) to assess the risk of bias in individual studies. RESULTS: We identified a total of 596 articles with 5 trials included in the final analysis. Exercise training was associated with an increase in VO2 max compared with no exercise training (mean difference, 3.95 [95% CI, 0.63-7.26]; I2 = 99.68%). Other cardiovascular outcomes such as LVEF (mean difference, 1.76 [95% CI, -1.95 to 5.46]; I2 = 99.44%), GLS (mean difference, 0.30 [95% CI, -0.49 to 1.10]; I2 = 96.63%), E/A ratio (mean difference, 0.05 [95% CI, -0.05 to 0.15]; I2 = 94.16%), and CO (mean difference, 0.38 [95% CI, -0.91 to 1.66]; I2 = 99.73%) are similar between patients who underwent exercise training and those who did not. CONCLUSIONS: Exercise was associated with an improvement in maximal oxygen uptake among women with breast cancer receiving anthracycline-based chemotherapy.

The relationship between statin administration timing and survival outcomes in patients with cancer receiving immune checkpoint blockade.

OBJECTIVE: Statins have been demonstrated to improve outcomes in patients receiving immune checkpoint blockade (ICB). This study aimed to investigate whether the timing of statin administration influences the outcomes of patients receiving ICB. METHODS: We conducted a retrospective cohort study utilizing electronic health records from two tertiary referral centers in Taiwan. We compared the overall survival (OS) and progression-free survival (PFS) of patients who received statins before and after ICB initiation. RESULTS: We included 734 patients who received ICB. Among them, 606 were non-statin users, 76 started statins after ICB initiation, and 52 started statins before ICB initiation. Post-ICB statin users demonstrated significantly prolonged OS (median 37.6 versus 10.3 versus 11.3 months, p = 0.009) and PFS (median 10.5 versus 6.3 versus 5.6 months, p = 0.024) compared to pre-ICB statin and non-statin users. Statin use after ICB initiation had a reduced risk of all-cause mortality (HR, 0.65 [95% CI: 0.45-0.94], p = 0.022) and progressive disease (HR, 0.71 [95% CI: 0.53-0.95], p = 0.021) by approximately 30-35%, compared to non-statin users. However, statin use prior to ICB initiation did not affect the risk of all-cause mortality or progressive disease. Similar results were observed after controlling for potential cofounders such as age, sex, cancer stage, and cancer type. CONCLUSIONS: These findings suggest that initiating statin therapy after the initiation of ICB, regardless of indication, is associated with improved patient prognosis.

The Efficacy of Cationic Amphiphilic Antihistamines on Outcomes of Patients with Pancreatic Ductal Adenocarcinoma.

BACKGROUND: Cationic amphiphilic H1-antihistamines have demonstrated antitumor effects in preclinical studies. We conducted a retrospective cohort study to investigate their impact on patients with pancreatic adenocarcinoma (PDAC). METHODS: We performed a matched cohort study involving PDAC patients from two tertiary centers in Taiwan using criteria including age, sex, and cancer stage. The primary outcome was overall survival (OS), and the secondary outcomes were progression-free survival (PFS) and objective response rates (ORR). RESULTS: We matched 28 cationic amphiphilic antihistamine users with 56 non-cationic amphiphilic antihistamine users. Cationic amphiphilic antihistamine users showed significantly longer OS (median 16.4 [IQR, 2.8 - 89.0] vs.5.8 [IQR, 2.0 - 9.8] months; p<0.001) and PFS (median 12.2 [IQR, 2.2 - 83.3] vs. 5.2 [IQR, 1.7 - 8.4] months; p=0.002) compared to non-users. In the Cox proportional hazard models, the use of cationic amphiphilic antihistamines was associated with approximately 60% lower risk of all-cause mortality and disease progression. Additionally, cationic amphiphilic antihistamine users exhibited a significantly greater ORR than non-users (39% vs. 7%, p=0.004). CONCLUSION: Our study suggests that cationic amphiphilic antihistamines are associated with improved survival outcomes in PDAC patients.

Efficacy of Lipophilic Statins on Outcomes of Patients Treated with Immune Checkpoint Inhibitors.

BACKGROUND: Statins are associated with improved survival outcomes in patients receiving immune checkpoint inhibitors (ICIs), but the impact of lipophilic and hydrophilic statin properties on patient outcomes is unknown. OBJECTIVES: We aim to investigate if statins with lipophilic properties are associated with clinical outcomes in patients receiving ICIs. METHOD: We conducted a retrospective cohort study at two tertiary referral centers in Taiwan comprising patients receiving ICIs between January 2015 and December 2021. We compared the comparative effect of lipophilic and hydrophilic statins on patient outcomes. The primary outcome was overall survival (OS) and the secondary outcome was progression-free survival (PFS). RESULTS: Among 734 patients receiving ICIs, there were 51 lipophilic statin users, 25 hydrophilic statin users, and 658 nonusers. Lipophilic statin users had a longer median OS (38.0 [IQR, 16.7-not reached] vs. 15.2 [IQR, 8.2-not reached] months vs. 18.9 [IQR, 5.4 51.6] months) and PFS (13.0 [IQR, 4.7-41.5] vs. 8.2 [IQR, 2.2-14.7] months vs. 5.6 [2.3-18.7] months) than hydrophilic statin users and non-statin users. In Cox proportional hazard analyses, the use of lipophilic statins was associated with a 40-50% lower risk of mortality and disease progression compared with hydrophilic statin or non-statin users. CONCLUSIONS: The use of lipophilic statins seems to be associated with survival benefits in patients undergoing immunotherapy.